scholarly journals Anti-diabetic effect of pyroglutamic acid in type 2 diabetic Goto-Kakizaki rats and KK-Aymice

2011 ◽  
Vol 106 (7) ◽  
pp. 995-1004 ◽  
Author(s):  
Orie Yoshinari ◽  
Kiharu Igarashi
Keyword(s):  
Glucose Tolerance ◽  
Therapeutic Potential ◽  
Serum Insulin ◽  
Pyroglutamic Acid ◽  
Oral Glucose ◽  
Gk Rats ◽  
Glucose And Lipid Metabolism ◽  
G6pase Activity ◽  
Vegetables And Fruits

With the rapidly increasing prevalence of type 2 diabetes mellitus (T2DM), specific dietary components with anti-diabetic efficacy could be one strategy with therapeutic potential. In the present study, the anti-diabetic effects of an amino acid, pyroglutamic acid (PA), found in vegetables and fruits were investigated in T2DM models using Goto-Kakizaki (GK) rats and KK-Aymice by measuring glucose tolerance and other markers of diabetes. Moreover, the effect of PA on gene expression in GK rats was measured by DNA microarray analysis. Oral glucose tolerance and serum insulin levels were reduced by PA in both animal models. Serum and liver total cholesterol levels were also improved by PA. Expression of genes involved with gluconeogenesis and those involved with its related transcription factor were down-regulated by feeding PA. In KK-Aymice, the glucokinase:glucose-6-phosphatase (G6Pase) activity ratio increased. From these results, it is suggested that dietary PA beneficially modifies glucose and lipid metabolism in diabetic animals, and can potentially contribute to the mitigation of T2DM.

scholarly journals Effects of Resveratrol in Goto-Kakizaki Rat, a Model of Type 2 Diabetes

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2488 ◽  
Author(s):  
Katarzyna Szkudelska ◽  
Marzanna Deniziak ◽  
Iwona Hertig ◽  
Tatiana Wojciechowicz ◽  
Marianna Tyczewska ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Pancreatic Islets ◽  
Lipid Accumulation ◽  
Therapeutic Potential ◽  
Gk Rats ◽  
New Findings

Resveratrol exhibits a pleiotropic, favorable action under various pathological conditions, including type 2 diabetes. However, its anti-diabetic effects in animal models and human trials have not been fully elucidated. The aim of the present study was to determine whether resveratrol is capable of inducing beneficial changes in the Goto-Kakizaki rat, a spontaneous model of diabetes, which in several aspects is similar to type 2 diabetes in humans. Goto-Kakizaki (GK) rats and control Sprague–Dawley (SD) rats were treated intragastrically with resveratrol (20 mg/kg b.w./day) for 10 weeks. Then, a glucose tolerance test was performed and levels of some adipokines in blood were measured. Moreover, lipid contents in skeletal muscle and liver tissues, along with the expression and phosphorylation of pivotal enzymes (AMP—activated protein kinase—AMPK, acetyl-CoA carboxylase—ACC, protein kinase B—Akt) in these tissues were determined. Histology of pancreatic islets was also compared. GK rats non-treated with resveratrol displayed a marked glucose intolerance and had increased lipid accumulation in the skeletal muscle. Moreover, upregulation of the expression and phosphorylation of AMPK, ACC and Akt was shown in the muscle tissue of GK rats. Those rats also had an abnormal structure of pancreatic islets compared with control animals. However, treatment with resveratrol improved glucose tolerance and prevented lipid accumulation in the skeletal muscle of GK rats. This effect was associated with a substantial normalization of expression and phosphorylation of ACC and Akt. In GK rats subjected to resveratrol therapy, the structure of pancreatic islets was also clearly improved. Moreover, blood adiponectin and leptin levels were partially normalized by resveratrol in GK rats. It was revealed that resveratrol ameliorates key symptoms of diabetes in GK rats. This compound improved glucose tolerance, which was largely linked to beneficial changes in skeletal muscle. Resveratrol also positively affected pancreatic islets. Our new findings show that resveratrol has therapeutic potential in GK rats.

scholarly journals Effect of breakfast fat content on glucose tolerance and risk factors of atherosclerosis and thrombosis

1998 ◽  
Vol 80 (4) ◽  
pp. 323-331 ◽  
Author(s):  
David L. Frape ◽  
Norman R. Williams ◽  
Jayshri Rajput-Williams ◽  
B. W. Maitland ◽  
A. J. Scriven ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Thrombus Formation ◽  
Serum Insulin ◽  
Lipid Fraction ◽  
Tolerance Test ◽  
Serum Glucose ◽  
Oral Glucose ◽  
Significant Treatment ◽  
Treatment Allocation ◽  
Insulin Responses

Twenty-four middle-aged healthy men were given a low-fat high-carbohydrate (5.5 g fat; L), or a moderately-fatty, (25.7 g fat; M) breakfast of similar energy contents for 28 d. Other meals were under less control. An oral glucose tolerance test (OGTT) was given at 09.00 hours on day 1 before treatment allocation and at 13.30 hours on day 29. There were no significant treatment differences in fasting serum values, either on day 1 or at the termination of treatments on day 29. The following was observed on day 29: (1) the M breakfast led to higher OGTT C-peptide responses and higher areas under the curves (AUC) of OGTT serum glucose and insulin responses compared with the OGTT responses to the L breakfast (P< 0.05); (2) treatment M failed to prevent OGTT glycosuria, eliminated with treatment L; (3) serum non-esterified fatty acid (NEFA) AUC was 59% lower with treatment L than with treatment M, between 09.00 and 13.20 hours (P<0.0001), and lower with treatment L than with treatment M during the OGTT (P= 0.005); (4) serum triacylglycerol (TAG) concentrations were similar for both treatments, especially during the morning, but their origins were different during the afternoon OGTT when the Svedberg flotation unit 20–400 lipid fraction was higher with treatment L than with treatment M (P= 0.016); plasma apolipoprotein B-48 level with treatment M was not significantly greater than that with treatment L (P= 0.086); (5) plasma tissue plasminogen-activator activity increased after breakfast with treatment L (P= 0.0008), but not with treatment M (P= 0.80). Waist:hip circumference was positively correlated with serum insulin and glucose AUC and with fasting LDL-cholesterol. Waist:hip circumference and serum TAG and insulin AUC were correlated with factors of thrombus formation; and the OGTT NEFA and glucose AUC were correlated. A small difference in fat intake at breakfast has a large influence on circulating diurnal NEFA concentration, which it is concluded influences adversely glucose tolerance up to 6 h later.

scholarly journals Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

2022 ◽  
Author(s):  
Marta Garaulet ◽  
Jesus Lopez-Minguez ◽  
Hassan S Dashti ◽  
Céline Vetter ◽  
Antonio Miguel Hernández-Martínez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Elevated Concentration ◽  
Endogenous Melatonin

<strong>Objective: </strong>We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (<i>MTNR1B</i>).<strong> </strong> <p><strong>Research Design and Methods:</strong> In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant <strong>(n=845) </strong>underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime <strong>(“early dinner-timing”)</strong>, and a late condition scheduled 1 hour prior to habitual bedtime <strong>(“late dinner-timing”)</strong>, simulating an early and a late dinner timing, respectively.<strong> </strong>Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between <strong>early and late dinner-timing.</strong><strong></strong></p> <p><strong>Results:</strong> <strong>Melatonin serum levels were </strong>3.5-fold <strong>higher in the late <i>vs. </i>early condition, with late dinner-timing resulting in </strong>6.7% <strong>lower insulin</strong> <strong>area-under-the-curve (AUC) and </strong>8.3%<strong> higher glucose</strong> <strong>AUC. In the late condition<i> MTNR1B</i> G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in </strong>β-cell <strong>function (<i>P<sub>int</sub></i><sub> </sub>AUCgluc=0.009, <i>P<sub>int</sub></i><sub> </sub>CIR=0.022, <i>P<sub>int </sub></i>DI=0.018).</strong></p> <p><strong>Conclusions:</strong> <strong>Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in <i>MTNR1B</i> G-risk-allele carriers<i>, </i>attributable to insulin secretion defects.</strong></p>

scholarly journals Long-term hyperglucagonaemia induces early metabolic and renal phenotypes of Type 2 diabetes in mice

2008 ◽  
Vol 114 (9) ◽  
pp. 591-601 ◽  
Author(s):  
Xiao C. Li ◽  
Tang-dong Liao ◽  
Jia L. Zhuo
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Weight Ratio ◽  
Glomerular Injury ◽  
Glucagon Receptor

Clinical studies have shown that patients with early Type 2 diabetes often have elevated serum glucagon rather than insulin deficiency. Imbalance of insulin and glucagon in favouring the latter may contribute to impaired glucose tolerance, persistent hyperglycaemia, microalbuminuria and glomerular injury. In the present study, we tested the hypothesis that long-term glucagon infusion induces early metabolic and renal phenotypes of Type 2 diabetes in mice by activating glucagon receptors. Five groups of adult male C57BL/6J mice were treated with vehicle, glucagon alone (1 μg/h via an osmotic minipump, intraperitoneally), glucagon plus the glucagon receptor antagonist [Des-His1-Glu9]glucagon (5 μg/h via an osmotic minipump), [Des-His1-Glu9]glucagon alone or a high glucose load alone (2% glucose in the drinking water) for 4 weeks. Glucagon infusion increased serum glucagon by 129% (P<0.05), raised systolic BP (blood pressure) by 21 mmHg (P<0.01), elevated fasting blood glucose by 42% (P<0.01), impaired glucose tolerance (P<0.01), increased the kidney weight/body weight ratio (P<0.05) and 24 h urinary albumin excretion by 108% (P<0.01) and induced glomerular mesangial expansion and extracellular matrix deposition. These responses were associated with marked increases in phosphorylated ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt signalling proteins in the liver and kidney (P<0.01). Serum insulin did not increase proportionally. Concurrent administration of [Des-His1-Glu9]glucagon with glucagon significantly attenuated glucagon-increased BP, fasting blood glucose, kidney weight/body weight ratio and 24 h urinary albumin excretion. [Des-His1-Glu9]glucagon also improved glucagon-inpaired glucose tolerance, increased serum insulin by 56% (P<0.05) and attenuated glomerular injury. However, [Des-His1-Glu9]glucagon or high glucose administration alone did not elevate fasting blood glucose levels, impair glucose tolerance or induce renal injury. These results demonstrate for the first time that long-term hyperglucagonaemia in mice induces early metabolic and renal phenotypes of Type 2 diabetes by activating glucagon receptors. This supports the idea that glucagon receptor blockade may be beneficial in treating insulin resistance and Type 2 diabetic renal complications.

scholarly journals Diagnosis and follow-up of type 2 diabetes in women with PCOS: a role for OGTT?

2018 ◽  
Vol 179 (3) ◽  
pp. D1-D14 ◽  
Author(s):  
Marianne Andersen ◽  
Dorte Glintborg
Keyword(s):  
Type 2 Diabetes ◽  
At Risk ◽  
Glucose Tolerance ◽  
Polycystic Ovary ◽  
Normal Weight ◽  
Oral Glucose ◽  
Diagnostic Purpose ◽  
Glycemic Status

Polycystic ovary syndrome (PCOS) is common in premenopausal women. The majority of women with PCOS have insulin resistance and the risk of type 2 diabetes mellitus (T2D) is higher in women with PCOS compared to controls. In non-pregnant women with PCOS, glycemic status may be assessed by oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) or HbA1c. OGTT has been reckoned gold standard test for diagnosing T2D, but OGTT is rarely used for diagnostic purpose in other non-pregnant individuals at risk of T2D, apart from PCOS. OGTT has questionable reproducibility, and high sensitivity of the 2-h glucose value is at the expense of relatively low specificity, especially regarding impaired glucose tolerance (IGT). Furthermore, lean women with PCOS are rarely diagnosed with T2D and only few percent of normal-weight women have prediabetes. Glycemic status is necessary at diagnosis and during follow-up of PCOS, especially in women with high risk of T2D (obesity, previous gestational diabetes (GDM)). We suggest that OGTT should be used in the same situations in PCOS as in other patient groups at risk of T2D. OGTT is indicated for diagnosing GDM; however, OGTT during pregnancy may not be indicated in lean women with PCOS without other risk factors for GDM.

Pre-diabetes and Type 2 Diabetes Status in Overweight and Obese Children in a Tertiary Care Hospital of Bangladesh

2021 ◽  
Vol 44 (3) ◽  
pp. 143-147
Author(s):  
Monira Hossain ◽  
Suraiya Begum ◽  
Shahana A Rahman
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Tertiary Care ◽  
Oral Glucose ◽  
Care Hospital ◽  
Obese Children ◽  
Diabetes Status

Introduction: Obesity in childhood is associated with many co-morbid conditions; one of them is alteration of glucose metabolism. Materials and Methods:This cross-sectional study was conducted among 100 overweight and obese children aged 5-16 years to determine the status of pre-diabetes (IFG and IGT) and type 2 diabetes mellitus (T2DM), attending the OPD, BSMMU, Dhaka. All overweight/obese children were included according to BMI for age and sex using CDC growth chart. Children taking steroid for any cause or having any endocrine disorder or syndrome was excluded from the study. Anthropometry and blood pressure measurement were done and skin manifestations of insulin resistance were looked for. Fasting lipid profile and oral glucose tolerance test (OGTT) was done for each child. Result: Among the studied children 62% were male and 38% female, 77% were obese and 23% were over weight. Evidence of insulin resistance were found among most of the children and most common evidence was dyslipidemia (80%) followed by acanthosis nigricans(76%). Skin manifestation of polycystic ovary syndrome (PCOS) was found in 3% of children. Impaired fasting glucose (IFG) was found in 4% and Impaired Glucose Tolerance (IGT) was found in 7% of children among them 4% had both IGT and IFT. No child was found diabetic in this study. Conclusion:Altered glucose metabolism was present in overweight and obese children of our children, so screening is recommended. Bangladesh J Child Health 2020; VOL 44 (3) :143-147

Chronic exercise increases insulin binding in muscles but not liver

1986 ◽  
Vol 251 (2) ◽  
pp. E196-E203
Author(s):  
A. Bonen ◽  
P. A. Clune ◽  
M. H. Tan
Keyword(s):  
Glucose Tolerance ◽  
Plasma Membranes ◽  
Serum Insulin ◽  
Exercise Bout ◽  
Insulin Binding ◽  
Tolerance Test ◽  
Time Of Day ◽  
Oral Glucose ◽  
Chronic Exercise ◽  
Binding Data

It has been postulated that the improved glucose tolerance provoked by chronic exercise is primarily attributable to increased insulin binding in skeletal muscle. Therefore, we investigated the effects of progressively increased training (6 wk) on insulin binding by five hindlimb skeletal muscles and in liver. In the trained animals serum insulin levels at rest were lower either in a fed (P less than 0.05) or fasted (P less than 0.05) state and after an oral glucose tolerance test (n = 8) (P less than 0.05). Twenty-four hours after the last exercise bout sections of the liver, soleus (S), plantaris (P), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG) muscles were pooled from four to six rats. From control animals, killed at the same time of day, muscles and liver were also obtained. Insulin binding to plasma membranes increased in S, P, and EDL (P less than 0.05) but not in WG (P = 0.07), RG (P greater than 0.1), or in liver (P greater than 0.1). There were insulin binding differences among muscles (P less than 0.05). Comparison of rank orders of insulin binding data with published glucose transport data for the same muscles revealed that these parameters do not correspond well. In conclusion, insulin binding to muscle is shown to be heterogeneous and training can increase insulin binding to selected muscles but not liver.

scholarly journals Risk of hypertension in middle-aged and elderly participants with newly diagnosed type 2 diabetes and prediabetes

2020 ◽  
Vol 8 (1) ◽  
pp. e001500
Author(s):  
Nobuo Sasaki ◽  
Ryoji Ozono ◽  
Ryo Maeda ◽  
Yukihito Higashi
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Fasting Glucose ◽  
Early Stage ◽  
Normal Glucose Tolerance ◽  
Oral Glucose ◽  
Newly Diagnosed ◽  
Middle Aged ◽  
Early Stages

IntroductionLittle is known about the risk of hypertension in patients with the early stage of type 2 diabetes. We investigated the risk of hypertension in participants with newly diagnosed type 2 diabetes and prediabetes.Research design and methodsThis is a retrospective cohort study consisting of 2136 middle-aged participants (1022 with normal fasting glucose/normal glucose tolerance (NFG/NGT), 418 with impaired fasting glucose (IFG), 466 with impaired glucose tolerance (IGT) and 230 with diabetes) and 3426 elderly participants (1762 with NFG/NGT, 599 with IFG, 781 with IGT, and 284 with diabetes). All participants underwent 75 g oral glucose tolerance tests at baseline.ResultsOver a median 59-month follow-up period, 459 middle-aged and 1170 elderly participants developed hypertension. In middle-aged participants, the odds of incident hypertension were significantly higher in those with IFG (OR 1.40; p=0.019), IGT (OR 1.49; p=0.004), and diabetes (OR 1.55; p=0.013) than those with NFG/NGT, which was no longer significant after adjustment for body mass index. Subgroup analysis showed that the risk of hypertension was significantly higher in diabetes than NFG/NGT only in participants without obesity. Conversely, obesity was a risk factor of hypertension only in those with IFG and NFG/NGT. In elderly participants, there was no difference in the risk of hypertension among the NFG/NGT, IFG, IGT and diabetes groups.ConclusionsThe risk of hypertension is modest in participants with newly diagnosed type 2 diabetes and prediabetes. Our findings suggest that the early stages of type 2 diabetes and prediabetes may be a key period for reducing hypertension, given the pronounced risk of hypertension in patients with diabetes reported in previous studies. In terms of reducing the risk for hypertension, obesity treatment might be advantageous in the early stages rather than the advanced stages of impaired glucose metabolism.

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